Stability of Clozapine Stored in Oral Suspension Vehicles at Room Temperature: Stability Study
The concentrations of clozapine observed in the various suspensions over the study period are presented in Table 1 (as percentage of original concentration). During the study period, the concentration of clozapine in all study samples remained within 5% of the initial concentration, and the inter-day variation in clozapine concentration (as assessed by CV) was less than 2.5%.
On the basis of the 95% CI for the fastest degradation rate, all samples retained at least 93.97% of the initial concentration. Multiple linear regression detected a significant (p = 0.0379) trend for a change in concentration during the 63-day study period, but this change averaged only 2.56%. Analysis of variance did not reveal any significant difference between suspension vehicles in the percentage remaining (p = 0.27); the largest difference between any 2 vehicles, with 95% confidence (Ora-Plus and the 1:1 mixture of Ora-Sweet and Ora-Plus), was 5.16%.
Figure 2. Representative chromatograms of clozapine in methanol (panel A) and during the stability study; panel B shows the chromatogram for a 20 mg/mL clozapine suspension in Guy’s pediatric mixture on study day zero, and panel C shows the same suspension on study day 63. One of the degradation products or impurities identified during the accelerated degradation study (eluting at 6.4 min) was observed in the chromatograms for both study day zero and study day 63. However, this peak did not change during the study period, and no other peaks observed during the accelerated degradation study were observed in any sample during the stability study.
Inspection of chromatograms obtained during the stability study revealed no increase in the concentration (peak height) of any degradation product or impurity that was observed during assay validation (Figure 2).
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All suspensions were initially opaque and light creamy-white and remained so for the duration of the study. Caking of clozapine was not apparent in any of the containers, an observation supported by the concentration analysis.